Photoreceptor signaling in primate retina

项目摘要/摘要 人类的日光视觉由中心凹的信号主导，这种专门化是白天活动的灵长类所特有的， 负责一半的视网膜输出，因此输入到高级视觉中心。我们的高清中央 视觉是由视锥感光器启动的，视锥感光器以密集而精致的像素阵列排列在中心凹中。 这种独特的安排与专门的视网膜电路一起是实现最高空间和色度的关键 归功于我们的中心愿景的决议。众所周知，视锥细胞感光细胞的密度和形态 中心凹和外围灵长类动物的视网膜明显不同，但我们对生理和 功能差异仍然相当差。有趣的是，我们最近对灵长类视网膜的观察揭示了 中心凹视锥信号的时间进程比外围视网膜慢两倍，这与 我们视锥细胞介导的视觉对高频闪光的时间敏感度存在两倍的差异。《博大》 我们项目的目标是确定视锥细胞信号的异质性的全部广度，“功能的视网膜复制”， 跨越一系列视觉输入和功能属性。我们将集中讨论三个突出的问题 目的：1)起源于灵长类锥体的信号在关键功能特性上有什么不同 视野中的光感受器？(2)视锥细胞光传导产生的细胞噪声是均匀的吗？ 视锥细胞穿过视野，它对视锥细胞的功能和知觉有什么限制？(3)中心凹视锥细胞 与其他灵长类动物视网膜中的视锥细胞相比，自然视觉期间的功能有何不同？我们会 使用电生理记录灵长类动物视网膜锥体的反应来回答这些问题 描述锥函数的模型。拟议的工作将提供对灵长类视锥细胞信号的详细洞察 尤其是在中心凹。视锥感光细胞死亡是视网膜疾病视力丧失的主要原因 攻击黄斑变性等中心凹。一种治疗这种退行性疾病的方法 疾病是干细胞衍生的光感受器替代疗法。我们的研究将提供急需的 关于中心凹视锥信号的基线信息用于评估人干细胞来源的视网膜的视锥功能 设计有效的基于干细胞的疗法，作为最终治愈退行性视网膜疾病的一种方式，如 黄斑变性等。

Project Summary/Abstract Human daylight vision is dominated by signaling in the fovea, a specialization unique to diurnal primates which is responsible for half of the retinal output and hence input to the higher visual centers. Our high-definition central vision is initiated in the cone photoreceptors which are packed in a dense and exquisite pixel array in the fovea. This unique arrangement together with the specialized retinal circuitry is key for the highest spatial and chromatic resolution attributed to our central vision. It is well known that the density and morphology of cone photoreceptors differ remarkably between foveal and peripheral primate retina, but our knowledge about the physiological and functional differences remain quite poor. Interestingly, our recent observations in primate retina have revealed that the time course of cone signals in the fovea is two-fold slower than in the peripheral retina consistent with the two-fold difference in the temporal sensitivity of our cone-mediated vision to high-frequency flicker. The broad goal of our project is to determine the full breadth of heterogeneities in cone signaling, “retinotopy of function”, across a range of visual inputs and functional properties. We will focus on three salient questions across three aims: 1) What are the differences in key functional properties of signals originating in the primate cone photoreceptors across the visual field? (2) Is cellular noise generated in cone phototransduction homogenous in cones across the visual field and what limits does it pose for cone function and perception? (3) Do foveal cones exhibit differences in function during natural vision compared to cones in rest of the primate retina? We will answer these questions using electrophysiological recordings of responses from cones in primate retina and models that describe cone function. The proposed work will provide a detailed insight into primate cone signaling especially in the fovea. Death of cone photoreceptors is the primary cause for vision loss in retinal diseases that attack the fovea such as macular degeneration. A therapy option that holds promise for such degenerative diseases is stem cell derived photoreceptor replacement therapy. Our study will provide the much-needed baseline information about foveal cone signaling to evaluate cone function in human stem cell derived retina for designing effective stem cell-based therapies as a way to ultimately cure degenerative retinal diseases such as macular degeneration and others.